Normal cells maintain a relatively low intra-cellular sodium concentration (10-40mM) against a large sodium pool in the extra- cellular space (120-150mM concentration). The large concentration gradient that develops across the cell membrane is critically important for maintenance of basic cellular functions and it is severely disrupted during the course of many pathological conditions. Disruption of this sodium gradient leads to a concomitant, and sometimes very specific, increase in intra-cellular sodium concentration. Thus, monitoring of changes in intra-cellular sodium content in vivo could provide valuable insights into specific aspects of in vivo cell metabolism during normal and diseased conditions. However, non-invasive tools for observing changes in intra-cellular sodium concentration are currently unavailable. Sodium MRI represents an attractive approach for the non-invasive monitoring of changes in sodium content in vivo. Although the NMR properties of the sodium nucleus had made sodium MRI very challenging, recent advances in MRI have made it possible to produce sodium images of diagnostic quality at clinical field strengths (1.5T) in times that are appropriate for routine clinical examinations. The sodium MRI methods demonstrated up to now can only provide quantitative maps of total tissue sodium concentration in vivo. The more demanding goal of producing in vivo maps of the intra-cellular tissue sodium concentration in humans remains a challenge, with exciting benefits, for which practical solutions can now be formulated using triple quantum (TQ) sodium imaging schemes. This R01 proposal is written in response to program announcement PA-99-009 (Biomedical Research Grants) and is aimed at developing an optimal methodology for in vivo, TQ sodium MRI in human brain. The goal is to design imaging schemes capable of producing TQ sodium images of diagnostic quality (SNR greater than 20:1, voxel size 1cc) in times acceptable for clinical studies (12 minutes). The proposed methodology is to be developed and tested on whole body clinical scanners and validated using phantom as well as in vivo data.